Individual effect-site concentrations of propofol at return of consciousness are related to the concentrations at loss of consciousness and age in neurosurgical patients

Nunes, Catarina S.; Ferreira, D.; Antunes, Luís; Lobo, Francisco; Santos, Isabel; Amorim, Pedro

doi:10.1016/j.jclinane.2008.06.011

Cited by 15 publications

(19 citation statements)

References 23 publications

(36 reference statements)

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“…When the effect of remifentanil C e on ROC was analyzed, we did not find a significant correlation, which is consistent with previous reports [13,14] . The C e of remifentanil (0.7±0.8 ng/mL) at ROC was probably too low to affect ROC.…”

Section: Discussionsupporting

confidence: 92%

A pharmacodynamic analysis of factors affecting recovery from anesthesia with propofol-remifentanil target controlled infusion

et al. 2012

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Aim: To examine individual patient's demographic parameters and clinical variables related to return of consciousness (ROC) and the pharmacodynamic relationship between propofol effect-site concentration (C e ) and ROC from propofol-remifentanil anesthesia. Methods: Ninety-four patients received propofol-remifentanil anesthesia using the effect-site target-controlled infusion (TCI) system. All clinical events were noted, and variables possibly related to propofol C e at ROC were examined using linear correlation analyses. Pharmacodynamic modeling incorporating covariates was performed using NONMEM (Nonlinear Mixed Effects Modeling) VII software. Results:The C e values of propofol at loss of consciousness (LOC) and ROC were 4.4±1.1 μg/mL and 1.1±0.3 μg/mL, respectively. Age was negatively correlated with propofol C e at ROC (r=-0.48, P<0.01). Including age as a covariate in C e50 (the effect-site concentration associated with 50% probability of return of consciousness) and λ (the steepness of the concentration-versus-response relationship) significantly improved the performance of the basic model based on the likelihood ratio test, with a significant decrease in the minimum value of the objective function. The C e50 in 25-, 50-, and 75-year-old patients was predicted to be 1.38, 1.06, and 0.74 μg/mL, respectively. The λ in 25-, 50-, and 75-year-old patients was predicted to be 12.23, 8.70, and 5.18, respectively. Conclusion: Age significantly affects the relationship between propofol C e and ROC, and pharmacodynamic modeling including age could lead to better predictions of ROC during emergence from propofol-remifentanil anesthesia.

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Section: Discussionsupporting

confidence: 92%

A pharmacodynamic analysis of factors affecting recovery from anesthesia with propofol-remifentanil target controlled infusion

et al. 2012

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“…Recently, models such as the Schnider model have been introduced into clinical practice. [1013] The Diprifusor Graseby Anesthesia Pump 3500 uses the Marsh model and was used in the present study. Anesthesiologists are instructed to enter the body weight and age into the settings of this pump; however, the age variable was not used to adjust the plasma and effect-site concentration predictions displayed by this pump.…”

Section: Discussionmentioning

confidence: 99%

“…showed that Cep values during ROC were related to the Cep values at LOC and patient age (19–76 years) and could be estimated by combining information of the Cep values at LOC and the patient's age. [10] However, whether an inter-relationship exists between Cep values at LOC and ROC in elderly patients undergoing elective surgeries is still unclear. There is no study investigating whether the differences in Ctarget values alter the similarity between individual Cep values at LOC and ROC.…”

Section: Introductionmentioning

confidence: 99%

The influence of initial target effect-site concentrations of propofol on the similarity of effect-sites concentrations at loss and return of consciousness in elderly female patients with the Diprifusor system

Shibuta

Kanemura

Uchida

et al. 2012

J Anaesthesiol Clin Pharmacol

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Background:Whether effect-site concentrations of propofol (Cep) at loss of consciousness and return of consciousness (LOC and ROC, respectively) in elderly women using Diprifusor are similar is unclear. We investigated whether differences in initial target Cep (Ctarget) alter similarities between Cep values at LOC and ROC.Materials and Methods:In this study, female patients (n = 58, age = 72.5 ± 1.1 years) undergoing knee arthroplasty were administered propofol with Diprifusor. Cep at LOC and ROC were estimated for different Ctarget values (3.0–4.5 μg/ml). Pearson's correlation coefficient analysis and simple regression were performed to assess the relationship between Cep at LOC and ROC for each Ctarget. Differences in correlation coefficients of regression lines obtained from each Ctarget group were determined using the t-test.Results:The different Ctarget groups did not show significant differences in total propofol levels and in Cep values at LOC or ROC. However, Cep at ROC was significantly higher than Cep at LOC when Ctarget was 4.0 and 4.5 μg/ml, whereas these Cep values were not significantly different in low Ctarget groups.Strong positive correlations were observed between Cep at LOC and ROC for all Ctarget groups. Regression coefficients for the different Ctarget groups were not significantly different. Compared to low (≤3.5 μg/ml) Ctarget groups, high Ctarget groups showed significantly shorter time until LOC. Induction quality was not significantly different among the groups.Conclusions:In elderly women, Cep values at LOC are strong predictors of Cep at ROC when Ctarget is 3.0–4.5 μg/ml. High Ctarget groups (≥4.0 μg/ml) exhibited shorter induction times with normal cardiovascular stability.

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“…ROC is defined as appearance of reaction in the patient to verbal stimulation, equivalent to an OAA/S scale change from 2 to 3. [11][12][13][14][15] The times elapsed from propofol injection to these two time points was recorded with a stopwatch as the time to LOC and to ROC, respectively.…”

Section: Methodsmentioning

confidence: 99%

Estimating the Plasma Effect-Site Equilibrium Rate Constant (<i>K</i><sub>e0</sub>) of Propofol by Fitting Time of Loss and Recovery of Consciousness

Sun

Wang

et al. 2013

Biological & Pharmaceutical Bulletin

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The present paper proposes a new approach for fitting the plasma effect-site equilibrium rate constant (Ke0) of propofol to satisfy the condition that the effect-site concentration (Ce) is equal at the time of loss of consciousness (LOC) and recovery of consciousness (ROC). Forty patients receiving intravenous anesthesia were divided into 4 groups and injected propofol 1.4, 1.6, 1.8, or 2 mg/kg at 1,200 mL/h. Durations from the start of injection to LOC and to ROC were recorded. LOC and ROC were defined as an observer's assessment of alertness and sedation scale change from 3 to 2 and from 2 to 3, respectively. Software utilizing bisection method iteration algorithms was built. Then, Ke0 satisfying the CeLOC=CeROC condition was estimated. The accuracy of the Ke0 estimated by our method was compared with the Diprifusor TCI Pump built-in Ke0 (0.26 min(-1)), and the Orchestra Workstation built-in Ke0 (1.21 min(-1)) in another group of 21 patients who were injected propofol 1.4 to 2 mg/kg. Our results show that the population Ke0 of propofol was 0.53 ± 0.18 min(-1). The regression equation for adjustment by dose (mg/kg) and age was Ke0=1.42-0.30 × dose-0.0074 × age. Only Ke0 adjusted by dose and age achieved the level of accuracy required for clinical applications. We conclude that the Ke0 estimated based on clinical signs and the two-point fitting method significantly improved the ability of CeLOC to predict CeROC. However, only the Ke0 adjusted by dose and age and not a fixed Ke0 value can meet clinical requirements of accuracy.

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Individual effect-site concentrations of propofol at return of consciousness are related to the concentrations at loss of consciousness and age in neurosurgical patients

Cited by 15 publications

References 23 publications

A pharmacodynamic analysis of factors affecting recovery from anesthesia with propofol-remifentanil target controlled infusion

A pharmacodynamic analysis of factors affecting recovery from anesthesia with propofol-remifentanil target controlled infusion

The influence of initial target effect-site concentrations of propofol on the similarity of effect-sites concentrations at loss and return of consciousness in elderly female patients with the Diprifusor system

Estimating the Plasma Effect-Site Equilibrium Rate Constant (<i>K</i><sub>e0</sub>) of Propofol by Fitting Time of Loss and Recovery of Consciousness

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